Our analysis of events in immediate hypersensitivity focuses on human and animal models of allergic responses, mechanisms of meditor action, and pharmacologic approaches to allergic diseases. Immediate hypersensitivity reactions are followed by late phase allergic responses (LPR), for which a rodent model has been developed. LPR require the participation of neutrophils for full expression and may be prevented by pretreatment with H-1 and H-2 antihistamines. In order to examine histamine responses, histamine receptors on human neutrophils, lymphocytes, and purified lung membranes have been quantified. All three tissues have a large number of relatively high affinity H-1 receptors. Very specific and sensitive assays for histamine reveal that urine histamine increases significantly after intravenous radiocontrast media and plasma histamine levels are constantly elevated in systemic mastocytosis. An assay for nasal blood flow has been developed employing laser-doppler velocimetry. Allergic rhinitis subjects have the same blood flow as normals, blood flow is reduced by alpha adrenergic agonists and not affected by cholinergic stimulation. In vivo analysis of vascular permeability may be a unique approach to the study of urticaria; therefore, measurement of vascular leakage of proteins and dextrans of several sizes has been developed. A model for depletion of mast cells involving ricin linked to myeloma IgE has been developed.